The Social Ladder’s Genetic Footprint

From the teenage years through adulthood, people spend a lot of time worrying about their social status. Whether measured in wealth as economic class or by more abstract terms of leadership and popularity in the office or among friends, social standing can weigh heavily upon a person’s mind. But can an individual’s position in their social network also leave a mark on biology, changing the regulation of genes and the strength of immune defenses against disease? Exciting new research conducted in one of our close primate relatives suggests that social factors can indeed penetrate deep into DNA.

In both their natural habitat, rhesus macaque monkeys organize into a hierarchical social system based on the results of competition for food, the best grooming buddies, and (in the wild) sexual partners. At the Yerkes National Primate Research Center in Atlanta, females housed in groups of five also organize into a dominance ranking, based on order of introduction to the group.

“In the wild, females would not ordinarily leave the social group they were born into,” said Jenny Tung, a former postdoctoral researcher in the laboratory of Yoav Gilad at the University of Chicago Department of Human Genetics. “They inherit their social rank from their mothers. But in this unnatural situation, order of introduction determines rank — the newcomer is generally lower status.”

That well-defined social system gave Tung, now an assistant professor of evolutionary anthropology at Duke University, and a team of collaborators the rare opportunity to look at how social status affects gene expression — and how that relationship is affected by a change in social rank. Other scientists had previously looked at the influence of social factors on gene regulation in species such as honeybees and cichlids, but nobody had looked in animals closer to humans on a genome-wide scale.

In a paper published by PNAS, the researchers used gene chips and blood samples to compare high-ranking monkeys to their low-ranked peers on the expression of nearly 6,000 genes. A significant difference was found for 987 of those genes, with the largest representation (112 genes) coming from the immune system. The result fits with data in monkeys where low rank and chronic stress lead to compromised immune function, and, more loosely, with human studies such as the legendary Whitehall Study that linked low socioeconomic status and high social stress to elevated disease risk.

The occasional transfer of monkeys from one social group to another at Yerkes offered the researchers another experimental opportunity. When a high-ranking female is removed from a group, the remaining monkeys benefit from an increase in rank. So researchers could compare gene expression before and after the rank shifts, and test whether the genetic “signature” of social status changed enough to predict their new position.

“We were able to use gene expression to classify individuals based on their rank,” said Gilad, associate professor of human genetics at the University of Chicago Biological Sciences and senior author of the study published in PNAS. “Demonstrating these very plastic and temporal changes was novel and quite interesting.”

The researchers were also able to look at potential mechanisms by which social status could influence genetic regulation. Two previously observed mechanisms — the activity of the stress hormone glucocorticoid system and changes in the cell composition of the blood samples — were both found to contribute to the gene expression differences between high and low ranking monkeys.

But a new, third mechanism was also described: the reversible shutdown of genes through DNA methylation. When a methyl group is added to a gene, it effectively turns that gene off. The researchers found a significant association between social rank and methylation on the 987 genes exhibiting expression changes, suggesting that this epigenetic modification contributes to the interaction of social status and genetic regulation.

“That’s a novel mechanism that people haven’t considered in primates,” Gilad said. “I know that some have been resistant to the possibility of methylation changes on this timescale, but this is a demonstration that this mechanism also matters.”

Beyond the biological nuts and bolts, the study raises a provocative question: is a lower social status actually bad for your health?

It’s far too speculative to apply the current study’s results to people, Tung and Gilad cautioned, and studying a similar relationship in human society — which doesn’t organize into a clean, measurable dominance hierarchy — would be nearly impossible due to confounding factors. But whatever influence social factors do have on human genetic regulation, the rhesus macaque study does offer at least one optimistic message, the authors agreed.

“There’s a spooky side to this kind of research, in that an individual’s social rank is partially determining health status,” Tung said. “But there’s also a hopeful side. For the seven females that changed ranks, their gene status changed with them. They’re not stuck in place, and I think that says something more broadly about the capacity for change.”

“An encouraging message to humans is the fact that the effects are plastic, reversible and change on a really large scale when rank changes,” Gilad said. “Whatever it is that causes stress through social environment, you might be able to fix.”